The present disclosure relates to magnetic resonance imaging. More particularly, the present disclosure relates to methods of collagen detection using magnetic resonance imaging systems.
Myocardial fibrosis is defined by increased collagen synthesis in the heart by fibroblasts and myofibroblasts, either in a local or diffuse distribution [1]. Of particular interest is diffuse myocardial fibrosis, which presents an imaging challenge due to the uniform interspersion of collagen throughout the myocardium. While diffuse myocardial fibrosis is a normal process of aging, it is accelerated in diseases, including aortic stenosis, cardiomyopathy, and hypertension [2]. Collagen volume fractions of 10-40% may result from diffuse myocardial fibrosis [3], compared to the 2-6% collagen volume fraction of a normal heart [3], [4]. The consequence is impaired ventricular systolic function and stiffness, ultimately leading to heart failure [1], [5]. Heart failure is a widely prevalent disease, estimated to affect 500,000 Canadians, and carrying a five-year survival rate of 50% [6].
In order to prevent late-stage heart failure, there is a need for a non-invasive and accurate measure of diffuse myocardial fibrosis. The gold standard for the diagnosis of diffuse myocardial fibrosis is endomyocardial biopsy, which measures the collagen volume fraction to evaluate the disease extent; however, this method is invasive and susceptible to sampling error [7]. Cardiovascular magnetic resonance (CMR) techniques have shown promise for the characterization of myocardial fibrosis, and include late gadolinium enhancement (LGE) and T1 mapping. Nevertheless, LGE is unsuitable for the detection of diffuse myocardial fibrosis, as the uniform distribution of collagen renders it difficult to achieve a clear signal intensity difference between healthy and fibrotic tissue [8]. T1 mapping with gadolinium-based contrast agents, by contrast, can be used to measure the extracellular volume fraction in diffuse myocardial fibrosis [9], [10]; however, this method is governed by gadolinium kinetics and is not specific to collagen [1], [7]. An imaging technique that can directly detect and quantify collagen would, hence, be of benefit to the diagnosis of diffuse myocardial fibrosis.
Ultra-short echo time (UTE) is an intrinsic MR contrast technique that can detect tissues with short T2* relaxation times, which are normally indiscernible using conventional pulse sequences. As collagen has a short T2*, this technique has been employed to image many collagen-containing tissues, including tendon, cartilage, ligaments, menisci, and bone. Ultra-short TEs are typically less than a few ms (e.g. 2 ms) where the lowest TE achievable is limited by the delay in switching between the radiofrequency excitation and the data acquisition. Recent literature by De Jong et al. [12] and Van Nierop et al. [13], [14] has demonstrated the feasibility of detection of myocardial fibrosis using UTE MRI. Using an MR image subtraction method, De Jong et al. and Van Nierop et al. showed that UTE MRI can be used for the qualitative delineation of myocardial infarct at 7 T and 9.4 T, respectively [12], [13].
The study of De Jong et al. predicted that the collagen short T2* component originated from the hydration layer water surrounding collagen [12]. In a different study, Van Nierop et al. modelled diffuse myocardial fibrosis quantitatively using a three-component T2* model at 9.4 T [14]. Van Nierop et al. found a signal with a short T2* of ˜0.8 ms and a chemical shift of ˜3 ppm, which they attributed to lipids.